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At least 451 records · Page 25Linked to original sources
PubMed1994

High [Ca2+]o-induced electrical heterogeneity and extrasystolic activity in isolated canine ventricular epicardium. Phase 2 reentry.

BACKGROUND: Elevated intracellular calcium activity is thought to play an important role in arrhythmia induction, particularly during ischemia and reperfusion. Delayed after-depolarization-induced triggered activity and intracellular communication problems are thought to be responsible. METHODS AND RESULTS: Increased extracellular calcium levels and rapid pacing are interventions known to elevate intracellular calcium activity. The present study, conducted using standard microelectrode techniques, was designed to compare the effects of increased [Ca2+]o (1.8 to 5.4 mmol/L) in isolated canine ventricular epicardial and endocardial tissues and to test the hypothesis that elevated intracellular calcium activity contributes to arrhythmogenesis in working ventricular myocardial tissues by promoting electrical heterogeneity. High [Ca2+]o caused a slight abbreviation of action potential duration (APD90) in endocardium but more dramatic rate-dependent and dynamic changes in epicardium. Under steady-state conditions, epicardium displayed a marked abbreviation of APD90 at fast rates but no significant changes at slow rates. A significant augmentation of phase 1 was evident at the faster stimulation rates. Vmax and conduction velocity were only slightly reduced. The marked abbreviation of the epicardial response at the factor rates was due to loss of the action potential dome. Recovery of the dome after deceleration was not synchronous throughout the preparation. As a consequence, a sudden slowing of rate caused marked dispersion of repolarization among neighboring epicardial sites, giving rise to ectopic activity via a phase 2 reentry mechanism. These effects of high [Ca2+]o were mimicked by exposure of the preparations to low [Na+]o. Electrical homogeneity was restored and arrhythmias were abolished after addition of the Ito blocker 4-aminopyridine 1 mmol/L. 4-Aminopyridine also eliminated the differential response of epicardium and endocardium to high [Ca2+]o. CONCLUSIONS: Our data demonstrate the induction of marked electrical heterogeneity and reentrant activity by high [Ca2+]o and rapid stimulation, conditions known to elevate [Ca2+]i. The results suggest that increased intracellular calcium activity, as occurs during ischemia and reperfusion, may contribute to the development of electrical inhomogeneity in the ventricle and thus to the genesis of ventricular arrhythmias through a mechanism other than triggered activity, namely, phase 2 reentry. Our data point to an increase in net outward current as the underlying mechanism for the calcium-induced changes. Our results also suggest that the presence of a prominent transient outward current (Ito) in epicardium sensitizes that tissue to the effects of high calcium. Finally, the results suggest that Ito blockers can reverse high calcium-induced electrical heterogeneity and thus can exert antiarrhythmic actions.

Action Potentials↗
PubMed2002

Sympathetic response to ventricular extrasystolic beats in hypertension and heart failure.

Provoked premature ventricular contractions (PVCs) evoke, in concomitance with an early and late blood pressure fall and overshoot, an early sympathoexcitation and a later period of sympathoinhibition, respectively. The present study was designed to examine whether in healthy subjects this is the case for spontaneous PVCs. Because of their pathophysiological relevance for arrhythmogenesis, it was also designed to determine whether the sympathetic responses are different from those seen in essential hypertension and congestive heart failure. In 14 untreated mild essential hypertensives (EH; age, 53.8+/-2.6 years; mean+/-SEM), 20 untreated congestive heart failure patients (CHF; age, 56.7+/-2.5 years; New York Heart Association class, II or III), and 16 age-matched healthy subjects (control) in Lown class <II, we evaluated the blood pressure (Finapres), heart rate (ECG), and muscle sympathetic nerve traffic (MSNA; by microneurography) responses to isolated monofocal PVCs. MSNA, quantified as bursts/100 heart beats, was significantly increased in EH (57.8+/-3.8, P<0.05) and CHF patients (77.7+/-4.0, P<0.01) compared with controls (44.6+/-4.4). In controls, the PVC-induced blood pressure fall and overshoot were accompanied by a sympathoexcitation (144.2+/-14%), followed by a period of sympathoinhibition (average duration, 12043+/-985 ms). The responses were similar in EH but not in CHF, in whom the magnitude of the sympathoexcitation and particularly the duration of the subsequent sympathoinhibition were strikingly reduced (average reduction, -46.1 and -72.8%, respectively). The most important factor accounting for this reduction appeared to be an altered baroreflex response to the PVC-induced BP changes. These data demonstrate that the MSNA responses to spontaneous PVCs are similar in controls and EH but markedly impaired in CHF, presumably because of the baroreflex alteration. This may represent an important factor for the genesis of the life-threatening ventricular arrhythmias that characterize CHF.

Aged↗
PubMed1979

Central serotonergic agents raise the repetitive extrasystole threshold of the vulnerable period of the canine ventricular myocardium.

Systemic administration of three central serotonergic agents, melatonin, 5-methoxytryptophol, and 6-chloro-2-(1-piperazinyl)-pyrazine (MK-212), produced significant increases in the threshold of the vulnerable period for repetitive electrical activity in the canine cardiac ventricle. MK-212 was effective despite bilateral vagotomy. The specific serotonin antagonist, metergoline, blocked the effect of MK-212 on the threshold. An increase in central serotonergic activity may inhibit the flow of arrhythmogenic sympathetic nerve traffic from the brain to the heart.

Animals↗
PubMed1993

Investigation of clinical characteristics of ventricular extrasystole in children--using two dimensional RR interval plotting method.

Eighty-three children were monitored by Holter electrocardiography for ventricular premature contraction (VPC), and the relationship between the preceding RR interval and the coupling interval was plotted using a two-dimensional RR interval plotting method. With this method, the slope (a) and standard deviation (SD) of the linear regression (Y = aX+b) were determined. These parameters were used to classify the patients into one of two types: a fixed type (SD < 40 msec, a < 0.2) and an unfixed type. The unfixed type was further divided into four subtypes, based on the plotted morphology: scattered, dependent, biphasic, and intermediate. The relationships between the VPC origin, organic heart disease, ventricular tachycardia (VT) and parasystole were investigated in the five types. The fixed and dependent types comprised significantly greater proportions of the subjects with VPC of right ventricular origin than of subjects with VPC of left ventricular origin (fixed: 31/59 right VPC vs 4/24 left VPC, p < 0.005; dependent: 13/59 vs 1/24, p < 0.05). On the other hand, comparatively very few subjects of the scattered type showed right VPC (4/59 vs 18/24, p < 0.005). Finally, the biphasic and intermediate types were distributed fairly equally among the subjects with VPCs of right and left ventricular origin (biphasic: 5/59 vs 0/24, p = 0.31, intermediate: 6/59 vs 1/24, p = 0.67). Organic heart disease was present in 13 subjects (15.7% of total subjects), seven of whom were of the fixed type with right ventricular origin (22.6% of subjects of this type). VT was observed in 34 subjects, but was rare in the scattered type (2/22 subject, 9.1%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗